Brief Summary

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a complex neuropsychiatric disorder characterized by the abrupt onset of symptoms and currently diagnosed mainly on clinical criteria, as reliable diagnostic biomarkers are still lacking. The primary objective of this project is to identify and validate a panel of neurophysiological, molecular, genetic, and metabolomic biomarkers associated with disease onset, clinical trajectory, and response to antimicrobial, anti-inflammatory, and immunomodulatory treatments. Identifying objective biomarkers will improve diagnostic accuracy, facilitate earlier diagnosis, clarify disease mechanisms, and support the development of more targeted therapeutic strategies.

PANS is currently considered a multifactorial immune-mediated inflammatory brain disorder resulting from the interaction of genetic susceptibility, immune dysregulation, infections, and environmental factors such as stress or trauma. Current evidence suggests that both innate and adaptive immune responses contribute to disease pathophysiology through interactions between the peripheral immune system and the central nervous system.

The pathogenic process may begin during fetal life through Maternal Immune Activation (MIA), whereby maternal infections or immune dysregulation induce inflammatory responses that increase susceptibility to neurodevelopmental disorders. During the postnatal period, infectious agents, including viruses, Mycoplasma pneumoniae, and Haemophilus influenzae, may trigger immune activation, leading to blood-brain barrier disruption, glial activation, and abnormalities within cortico-basal ganglia circuits thought to underlie PANS symptoms.

To achieve these objectives, the project will adopt a multidisciplinary translational approach that combines the enrolment and characterization of pediatric patients with PANS with complementary studies in animal models. Particular emphasis will be placed on clinical and sleep features, together with molecular and metabolomic profiling, to identify biomarkers with diagnostic and prognostic value and to investigate the biological pathways underlying disease onset and progression.

Given the high clinical, social, and economic burden of PANS, which frequently follows a chronic or relapsing-remitting course requiring long-term healthcare support, earlier diagnosis and a better understanding of disease mechanisms could significantly improve patient management. More broadly, the project will contribute to understanding the immune-mediated pathogenic pathways underlying PANS and related neurodevelopmental disorders, supporting the transition from symptom-based classification toward mechanism-based diagnosis and treatment.

Conditions

• PANS
• Pediatric Acute-Onset Neuropsychiatric Syndrome

Intervention / Treatment

• Diagnostic Test: Psycodiagnostic evaluation
• Diagnostic Test: Polysomnography
• Diagnostic Test: 1H-NMR analysis
• Diagnostic Test: miRNA sequencing

Primary Outcome Measures

• Concentrations of predefined inflammatory biomarkers (From the enrollment through study completion, an average of 36 months)
  Inflammatory biomarker concentrations will be measured in biological samples using predefined laboratory assays. Associations between biomarker concentrations and psychiatric, neuropsychological, and polysomnographic measures will be evaluated using predefined statistical analyses.

Countries

Italy

Locations and Investigators

• Centro di Medicina del Sonno, SC Neurologia, AOU Cagliari, Cagliari, Italy (Active not recruiting)
• Università degli Studi eCampus, Novedrate, Italy (Active not recruiting)
• UOC Neuropsichiatria, Troina, Italy (Active not recruiting)
• Azienda Ospedaliera Universitaria Gaetano Martino, Messina, Italy (Recruiting)
  • Eva Germanò, MD, PhD
• Dipartimento di Scienze Psicologiche, Pedagogiche, dell¿Esercizio Fisico e della Formazione, Palermo, Italy (Active not recruiting)